Voriconazole and Buprenorphine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Voriconazole
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Here's what's going on. Voriconazole is an antifungal medicine that slows down a liver enzyme (called CYP3A4) that normally breaks down your buprenorphine. When that breakdown slows, more buprenorphine builds up in your body. That can make its effects stronger and last longer, including too much sleepiness and slowed breathing.
On top of that, both medicines can affect your heart's rhythm (a change called QT prolongation), and using them together adds to that risk.
The good news: this is very manageable. Keep taking both exactly as prescribed, and your care team can adjust your buprenorphine dose and watch you more closely. Call them right away if you feel unusually drowsy, confused, or short of breath.
Mechanism: Voriconazole is a potent CYP3A4 inhibitor and reduces buprenorphine metabolism, increasing buprenorphine exposure (Cmax/AUC). Buprenorphine is an active drug, not a prodrug, so inhibition intensifies opioid effect. Both agents independently prolong the QT interval, giving additive cardiac risk.
Direction: increased buprenorphine effect and additive QTc prolongation. Evidence: probable. Onset: unspecified.
Management:
- Monitor for sedation and respiratory depression; consider reducing buprenorphine dose until stable.
- Obtain/monitor ECG for QT prolongation, correct electrolytes.
- On voriconazole discontinuation, anticipate a buprenorphine dose increase and monitor for withdrawal.
- Use formulations allowing precise titration if needed.
What happens
An increased risk of QT interval prolongation, increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
Combining buprenorphine with a CYP3A4 inhibitor can raise buprenorphine plasma concentrations, which may lead to extended opioid effects such as respiratory depression. The concurrent use of agents that alter cardiac conduction also heightens the likelihood of QT prolongation. When these are used together, watch the patient carefully for signs of a lengthened QT interval. It may be appropriate to lower the buprenorphine dose until steady drug effects are reached, along with frequent monitoring for sedation and respiratory depression. Should a CYP3A4 inhibitor be stopped in a patient on buprenorphine, an increase in the buprenorphine dose may be warranted until stable effects are established, with monitoring for indications of opioid withdrawal2. When the dose cannot be modified once the CYP3A4 inhibitor is no longer present, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients transitioned from transmucosal buprenorphine given alongside CYP3A4 inhibitors, confirm through monitoring that the buprenorphine plasma level achieved with subQ buprenorphine is sufficient. For those already receiving subQ buprenorphine who need a CYP3A4 inhibitor, observe for signs and symptoms of over-medication. If buprenorphine toxicity or overdose manifestations appear yet the accompanying medication cannot be lowered or stopped, decrease the buprenorphine dose. When the available doses cannot deliver the intended dose, stop treatment and manage the patient with a buprenorphine formulation that permits more precise dose adjustments 1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable with the right monitoring.
Your team may:
- Adjust and individualize your buprenorphine dose until your effects are stable.
- Watch you more closely for sedation and slowed breathing.
- Check your heart rhythm (an ECG) because both drugs can affect QT.
- Plan to raise your buprenorphine dose again when voriconazole is stopped, watching for withdrawal.
Call your pharmacist or prescriber if you feel very drowsy, confused, dizzy, or have trouble breathing or a pounding/irregular heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a trial involving healthy volunteers (N=12), giving oral buprenorphine together with voriconazole produced a significant rise in the mean buprenorphine AUC(0 to 18 hours), increasing it 4.3-fold (from 0.43 to 2.1 nanograms (ng) x hr/mL), a 3.9-fold increase in Cmax (from 0.057 to 0.22 ng/mL), a longer half-life (from 9.1 to 14.5 hours), and greater urinary clearance (from 0.31 to 0.73 L/hr). Voriconazole likewise significantly raised exposure to the active metabolite norbuprenorphine, with AUC(0 to 18 hours) increasing by nearly 4-fold and Cmax by 3.3-fold, while decreasing renal clearance (from 7.2 to 2.9 L/hr). Participants had mild dizziness and nausea in both phases. Subjects were given either placebo or voriconazole 400 mg twice daily on day 1 and 200 mg twice daily on days 2 to 5, followed by a 4-week washout period before crossing over to the alternate regimen. On the fifth day, every subject received a single oral dose of buprenorphine 0.2 mg, or 3.6 mg during the placebo phase 3.
b) The impact of concurrently administered CYP3A4 inhibitors on buprenorphine exposure in patients receiving subQ buprenorphine has not been investigated; nevertheless, such interactions have been documented in studies that used transmucosal buprenorphine. The effects of buprenorphine may vary according to the route of administration 1.
Common questions
Can I take Voriconazole and Buprenorphine together?
Voriconazole can raise buprenorphine levels and both can affect heart rhythm, so watch for excess sedation, slowed breathing, and QT changes. Keep taking both as prescribed and let your care team adjust the buprenorphine dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Voriconazole and Buprenorphine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Voriconazole and Buprenorphine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable with the right monitoring. Your team may: Adjust and individualize your buprenorphine dose until your effects are stable. Watch you more closely for sedation and slowed breathing. Check your heart rhythm (an ECG) because both drugs can affect QT. Plan to raise your buprenorphine dose… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Voriconazole or Buprenorphine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: ZUBSOLV(R) sublingual tablets, buprenorphine naloxone sublingual tablets. Orexo US Inc (per FDA), Morristown, NJ, 2023. DailyMed
- Fihlman M, Hemmila T, Hagelberg NM, et al: Voriconazole greatly increases the exposure to oral buprenorphine. Eur J Clin Pharmacol 2018; 74(12):1615-1622. PubMed
Keep reading about Buprenorphine
Keep reading about Voriconazole
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